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Fears of vCJD timebomb revived

A “significant number” of people in the UK may be harbouring vCJD with no clinical symptoms, reveals the study of a new case. The work suggests the epidemic of the human form of mad cow disease may be far from over.

The second case of vCJD linked to a blood transfusion was announced by the UK department of health on 22 July. But investigations have now revealed that this person, who had no clinical symptoms and died from other causes, is the first case of vCJD to be found in the largest genetic subgroup of the population.

The discovery has major implications for the ultimate extent of the vCJD epidemic, as about 50 per cent of the UK population falls into this group.

“What this finding now indicates is that the largest genetic subgroup is susceptible to this infection,” warns James Ironside, director of the UK’s National CJD Surveillance Unit in Edinburgh, UK, and one of the study team. “From one case you can’t extrapolate too far but it seems that many of them are likely to be infected.”

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This is because exposure to vCJD by eating infected beef was “likely to be widespread” in the late 1980s and early 1990s, he says. The 142 deaths seen in the UK so far have affected people in a smaller subgroup, who may have a shorter incubation time.

Person-to-person

The case is also ominous because it is the second believed to be acquired through a person-to-person blood transfusion. Furthermore, the donor had not developed any symptoms of vCJD at the time of donation, showing such people can still transmit the disease.

The first transfusion case was identified in December 2003 in the UK. The patient died from vCJD seven years after receiving a blood transfusion from a donor who also later died of the disease.

“I don’t want to be alarmist about this – but this really is an important case,” Ironside told New Scientist. “Firstly, it means this genotype is susceptible; secondly, it clearly means vCJD is being harboured; and thirdly, the illness was almost certainly acquired as a result of a blood transfusion.”

He says the “secondary transmission” via blood transfusion also raises the issue of transmission via surgical instruments. No known cases of vCJD have been transmitted this way, but Ironside notes&colon; “Unfortunately, with this disease, if the worst can happen it apparently does.”

Common combination

In the latest case, the patient died from a non-neurological disorder five years after receiving blood from a donor who subsequently developed and died from vCJD. The patient was the one of 17 identified as having received blood from infected donors.

An autopsy revealed that the patient had the mutated prion proteins responsible for vCJD in the spleen, despite showing no symptoms of the devastating disease. These rogue proteins were not found in the brain, spinal cord, or tonsils.

Crucially, the patient is the first to have the commonest combination of genes for the normal prion protein. All vCJD deaths to date have occurred in people who have two identical genes – one each from their mother and father. But there is another version of the gene and the latest patient was “heterozygous”, i.e. they had one of each type.

Ironside says that because the number of vCJD cases peaked in 2000, “there was a view that may be this was the beginning of the end”. But the new case shows that heterozygous people may just be incubating the disease for longer.

That view is supported by studies of other similar diseases, like kuru in Papua New Guinea, which show that heterozygous people can incubate the diseases for a long time. “Incubation periods over several decades are not uncommon,” says Ironside.

Tonsil and appendix

Azra Ghani, an epidemiologist at Imperial College London, UK, who has been modelling the course of the vCJD epidemic agrees the discovery is of major importance. She estimates that if heterozygous people are similarly susceptible to those who are not, there might be a doubling of projected deaths.

Her group currently estimates 50 to 60 more cases in the UK by 2080, based on the numbers of real cases. However, she cautions that initial data from a survey of tonsil and appendix tissue suggests there may be 3800 more cases.

She also told New Scientist that the potential for blood transfusion to spread vCJD holds “greater uncertainty” as there are many unanswered questions&colon; “How infectious is blood? What sort of dose would you need?”

Unquantifiable risk

The UK’s Department of Health stepped up its precautionary measures for blood transfusion in December 2003 and again after the second case was announced in July.

John Reid, the secretary of state for health, stressed the “small but unquantifiable risk” at that time. “People should continue to have a blood transfusion when it is really necessary. Any slight risk associated with receiving blood must be balanced against the significant risk of not receiving it,” he said.

Ironside stresses the urgent need for a blood test to detect vCJD. If many people are incubating the disease, he warns, “we have no means of detecting them preclinically”.

“We should take some comfort from that fact that we have not seen a huge mass of epidemics in humans,” he says. “But the idea that vCJD’s going away now cannot be considered to be the case.”